Treatment of CNS disorders with trans 4-3(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine

Abstract

Treatment of central nervous system disorders with (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine and with (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine is disclosed. A process for preparing 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine is also disclosed.

1 . A method for treating an anxiety disorder in a human, the method comprising administering to a person in need of therapy for an anxiety disorder, a therapeutically effective amount of a compound chosen from (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (A); (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (B);  
       
         
           
           
               
               
           
         
       
       mixtures of A and B; and pharmaceutically acceptable salts thereof.  
     
     
         2 . The method according to  claim 1 , wherein the anxiety disorder is chosen from agoraphobia, generalized anxiety disorder, phobic anxiety, obsessive-compulsive disorder (OCD), panic disorder, acute stress disorder, posttraumatic stress disorder, premenstrual syndrome, social phobia, chronic fatigue disorder, perimenopause, menopause and male menopause.  
     
     
         3 . A method for treating an eating disorder in a human, the method comprising administering to a person a need of therapy for an eating disorder, a therapeutically effective amount of a compound chosen from (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (A); (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (B);  
       
         
           
           
               
               
           
         
       
       mixtures of A and B; and pharmaceutically acceptable salts thereof.  
     
     
         4 . The method according to  claim 3 , wherein the eating disorder is chosen from anorexia nervosa, bulimia nervosa, obesity and cachexia.  
     
     
         5 . A method for treating a condition chosen from disruptive behavior disorders, substance abuse and cerebral function disorders and disorders characterized by non-urge and urge incontinence in a human, the method comprising administering to a person in need of therapy for the chosen condition, a therapeutically effective amount of a compound chosen from (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (A); (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (B);  
       
         
           
           
               
               
           
         
       
       mixtures of A and B; and pharmaceutically acceptable salts thereof.  
     
     
         6 . A method for the prophylaxis of migraine in a human, the method comprising administering to a person at risk or in need of therapy for a migraine, a therapeutically effective amount of a compound chosen from (1R,4S)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (A); (1S,4R)-trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine (B);  
       
         
           
           
               
               
           
         
       
       mixtures of A and B; and pharmaceutically acceptable salts thereof.  
     
     
         7 . A process for preparing 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine comprising: 
 (a) reacting 4-(3,4-dichlorophenyl)-3,4-dihydro-1-naphthalenone with an excess of formic acid and formamide to provide N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen- 1-yl]formamide; and    (b) reducing the N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]formamide with a hydride reducing agent.    
     
     
         8 . The process according to  claim 7 , wherein the hydride reducing agent is borane.  
     
     
         9 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       wherein R is  
       
         
           
           
               
               
           
         
       
       and R 1 , R 2  and R 3  are each independently alkyl.  
     
     
         10 . A compound according to  claim 9 , wherein R is t-butyl.